The invention relates to the improvement of
endonuclease-based antimicrobials by blocking
DNA repair of double-strand break(s) (DSB(s)) in
prokaryotic cells. In this respect, the invention especially concerns a method involving blocking
DNA repair after a
nucleic acid has been submitted to DSB, in particular by a Clustered Regularly Interspaced Short Palindromic Repeats (
CRISPR) associated programmable double-strand
endonuclease. The invention particularly relates to the use of an exogenous molecule that inhibits
DNA repair, preferably a
protein that binds to the ends of the double-stranded break to block DSB repair. The invention also relates to vectors, particularly phagemids and plasmids, comprising nucleic acids encoding nucleases and Gam proteins, and a pharmaceutical composition and a product containing these vectors and their application.